Application of Open Porous Microspheres in Hepatic Tissue Cultivation
Date Issued
2010
Date
2010
Author(s)
Yeh, Peng-Lin
Abstract
Each year liver diseases have threatened people’s lives in Taiwan and many other countries. Alcohol, drug, virus-induced hepatitis, and malignant tumor can cause liver damage and result in liver failure. In the treatment of liver failure, liver transplantation has been established as an effective final option. For instance, the mortality rate of patients who suffered from acute liver failure (ALF) was reported as high as 80% without liver transplantation. However, due to the shortage of donated organ supply, hepatic tissue engineering, which includes hepatocyte transplantation, tissue-engineered grafts and liver assist devices (LADs), has been investigated for several decades in attempt to provide alternative approaches. One of the major obstacles of hepatic tissue engineering was the short-term viability and rapid de-differentiation of hepatocytes in vitro. Recent studies have indicated that combination of appropriate scaffold, factors, and co-culturing with other cell types may overcome this problem.
In this study, open porous poly (lactic-co-glycolic acid) (PLGA) microspheres were fabricated using gas foaming in a W1/O/W2 double emulsion method, with a mean size of approximately 430μm and an average pore diameter mostly between 10-20μm. Comparing with nonporous microspheres as scaffold, culturing hepatocytes with open porous microspheres provided suitable microenvironments for higher cell seeding density and exchange of nutrients, oxygen, and metabolites. Unlike porous scaffolds requiring open surgery process for implantation in the body, open porous microspheres can deliver cells with a syringe in an injectable manner, which is more patient-friendly. For further improvement in viability and specific hepatic functions, nonparenchymal cells (rat fibroblasts, rat mesenchymal stem cells and human umbilical venous endothelial cells) were each co-cultured with mature hepatocytes. Quantification of albumin secretion and urea synthesis showed that nonparenchymal cells may support hepatocellular functions due to cell-cell interactions or secretion of soluble factors.
This study suggested that open porous PLGA microspheres were successfully developed and used as the hepatocytes culturing scaffold. Moreover, the hepatocellular specific functions sustained up to 2 weeks in the support of co-culturing with nonparenchymal cells. Although the cell-cell interactions and soluble factors between hepatocytes and nonparenchymal cells requires further understanding, the combination of open porous microspheres, hepatocyes, and nonparenchymal cells co-culturing system has the potential in hepatic tissue engineering application.
Subjects
Hepatic tissue engineering
Gas foaming
PLGA microspheres
Hepatocytes
Albumin secretion
Urea synthesis
SDGs
Type
thesis
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